β1-Adrenoceptor in the Central Amygdala Is Required for Unconditioned Stimulus-Induced Drug Memory Reconsolidation.

β1-Adrenoceptor in the Central Amygdala Is Required for Unconditioned Stimulus-Induced Drug Memory Reconsolidation.
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无条件刺激诱导的药物记忆重建需要中央杏仁核中的β1-肾上腺素受体

DOI:
10.1093/ijnp/pyx104
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发表时间:
2018-03-01
期刊:
The international journal of neuropsychopharmacology
影响因子:
--
通讯作者:
Ma L
Ma L
中科院分区:
其他
文献类型:
--
作者:
Zhu H;Zhou Y;Liu Z;Chen X;Li Y;Liu X;Ma L

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药物记忆变得不稳定,并通过呈现环境线索(条件刺激)或药物(非条件刺激)进行检索后重新巩固。条件刺激和非条件刺激提取是否触发不同的记忆再巩固过程尚不清楚。在可卡因条件性位置偏爱或自我给药模型小鼠中,于可卡因再次暴露后立即给予蛋白合成抑制剂或β-肾上腺素能受体(β-AR)拮抗剂或杏仁核内注射。选择性地敲除杏仁核中央的β-AR,进一步证实β-肾上腺素能受体在可卡因抑制诱导的可卡因条件性位置偏爱记忆再巩固中的作用。可卡因再暴露触发可卡因条件性位置偏爱的从头蛋白质合成依赖性记忆再巩固。可卡因引发诱导的复吸也受损后可卡因检索操作,与背景检索操作后的复发行为。联想提取,而不是上下文提取,诱导中央杏仁核激活。在可卡因提取后,在中央杏仁核中注入蛋白质合成抑制剂或β1-肾上腺素能受体拮抗剂,而不是背景提取,抑制记忆的重新巩固和恢复。中央杏仁核β1-肾上腺素能受体敲除抑制可卡因提取触发的记忆再巩固和可卡因条件性位置偏爱的恢复可卡因回收后的β1-肾上腺素能受体拮抗作用也损害了可卡因自我给药的再巩固和恢复。非条件刺激提取触发的联想奖赏记忆不同于条件刺激提取。非条件刺激提取诱导可卡因奖赏记忆的再巩固依赖于中央杏仁核β1-肾上腺素能信号后非条件刺激提取操作可以防止药物记忆的再巩固和可卡因复吸,从而为预防物质成瘾提供了一种潜在的策略。众所周知,药物记忆在条件刺激(CS)或非条件刺激(US)的作用下变得不稳定并在提取时重新巩固。CS和US提取是否触发不同的记忆再巩固过程是未知的。在本研究中,我们发现US提取,而不是CS提取,触发可卡因条件性位置偏爱的记忆再巩固依赖于β1-AR和中央杏仁核的从头蛋白质合成。此外,可卡因引发诱导的恢复受损后US检索操作与复发行为后CS检索操作。在可卡因自身给药中,超声恢复后的β1-AR拮抗作用也损害了再巩固和恢复。我们的研究表明,可卡因奖励记忆的再巩固触发的US提取不同于CS提取。US提取诱导可卡因奖赏记忆的再巩固依赖于中央杏仁核中的β1-肾上腺素能信号
Drug memories become labile and reconsolidated after retrieval by presentation of environmental cues (conditioned stimulus) or drugs (unconditioned stimulus). Whether conditioned stimulus and unconditioned stimulus retrieval trigger different memory reconsolidation processes is not clear. Protein synthesis inhibitor or β-adrenergic receptor (β-AR) antagonist was systemically administrated or intra-central amygdala infused immediately after cocaine reexposure in cocaine-conditioned place preference or self-administration mice models. β-ARs were selectively knocked out in the central amygdala to further confirm the role of β-adrenergic receptor in cocaine reexposure-induced memory reconsolidation of cocaine-conditioned place preference. Cocaine reexposure triggered de novo protein synthesis dependent memory reconsolidation of cocaine-conditioned place preference. Cocaine-priming-induced reinstatement was also impaired with post cocaine retrieval manipulation, in contrast to the relapse behavior with post context retrieval manipulation. Cocaine retrieval, but not context retrieval, induced central amygdala activation. Protein synthesis inhibitor or β1-adrenergic receptor antagonist infused in the central amygdala after cocaine retrieval, but not context retrieval, inhibited memory reconsolidation and reinstatement. β1-adrenergic receptor knockout in the central amygdala suppressed cocaine retrieval-triggered memory reconsolidation and reinstatement of cocaine conditioned place preference. β1-adrenergic receptor antagonism after cocaine retrieval also impaired reconsolidation and reinstatement of cocaine self-administration. Cocaine reward memory triggered by unconditioned stimulus retrieval is distinct from conditioned stimulus retrieval. Unconditioned stimulus retrieval induced reconsolidation of cocaine reward memory depends on β1-adrenergic signaling in the central amygdala. Post unconditioned stimulus retrieval manipulation can prevent drug memory reconsolidation and relapse to cocaine, thus providing a potential strategy for the prevention of substance addiction. It is well known that drug memories become labile and reconsolidated upon retrieval by the presentation of conditioned stimulus (CS) or unconditioned stimulus (US). Whether CS and US retrieval trigger different memory reconsolidation processes is unknown. In this study, we found that US retrieval, but not CS retrieval, triggered memory reconsolidation of cocaine-conditioned place preference dependent on β1-AR and de novo protein synthesis in the central amygdala. Furthermore, cocaine priming-induced reinstatement was impaired with post US retrieval manipulation in contrast to the relapse behavior with post CS retrieval manipulation. In cocaine self-administration, β1-AR antagonism after US retrieval also impaired reconsolidation and reinstatement. Our study indicates that reconsolidation of cocaine reward memory triggered by US retrieval is distinct from CS retrieval. US retrieval induced reconsolidation of cocaine reward memory depends on β1-adrenergic signaling in the central amygdala.
从杏仁核中的电路到行为。
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发表时间: 2015-01-15
期刊: Nature
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